Vasopressin (VP) synthesized in the magnocellular-neurohypophysial (MC-NH) system and secreted from the posterior pituitary functions physiologically to regulate hydration via action on the kidney. VP may also regulate hydration by interaction with CNS target tissue(s). Current research suggests an interrelationship between the MC-NH and two brain circumventricular organs (subfornical organ, SFO; pineal gland) implicated to function in fluid regulation. The SFO: a) contains VP; b) has neural connections MC-NH; c) affects drinking behavior and sodium excretions; and d) releases an unidentified material altering fluid balance. The pineal gland secretes peptides into CSF which affect hydration and modulate MC-NH neurosecretory activity. The goal of the proposed research is to answer three questions: a) Is VP in the SFO an unrecognized part of the MC-NH system or independent of it? b) Is synthesis of VP in brain tissue responsive to dehydration and hormones of the renin-angiotensin system? c) Does the pineal gland regulate MC-NH secretion of VP? VP biosynthesis will be expressed as specific activity of VP (35S-VP; dpm/pg VP) after 35S-cysteine injection into: a) selective regions of the brain; b) cerebroventricular CSF; or c) an isolated tissue bath. VP will be measured by radioimmunoassay. The studies proposed will determine if: a) VP in the SFO is synthesized locally or transported from the MC-NH, in vitro; b) VP content or specific activity changes in plasma, the SFO area and MC-NH (anterior hypothalamus-MC nuclei; posterior lobe) during dehydration and after renin stimulation; c) VP in the SFO alters MC-NH neurosecretion of VP. Pineal gland-MC relationships will be determined as pinealectomy effects on diurnal salt-water-balance and VP in plasma, MC-NH and SFO area during dehydration. MC-NH secretion of VP for action on renal target tissue is a major physiological mechanism regulating salt-water-balance. However, VP may also interact with brain circumventricular organ(s), particularly the SFO. Elucidation of these cerebral interactions will provide knowledge of how the brain regulates blood pressure and hydration.